Although hormone replacement therapy (HRT) for postmenopausal women is associated with significant health benefits, it also carries a two- to fourfold increased risk of venous thromboembolism (VTE). This protocol is the first step toward determining whether this increased risk is concentrated in the population of women who carry either of two relatively common genetic risk factors for thrombosis, factor V Leiden (FVL) or hyperhomocysteinemia. We are exploring the feasibility of using a battery of laboratory parameters to assess the effect of HRT on coagulation and fibrinolysis in women with these traits. To do this we are first determining the time-dependent variability of these parameters in women with FVL or hyperhomosteinemia as well as in control women to see whether HRT-related effects are likely to be detected using realistically achievable numbers of study subjects. Therefore, we are screening as many as 300 postmenopausal women to identify ten who have FVL and ten who have hyperhomocysteinemia as their only risk factor for thrombosis and 20 control women. These three groups undergo extensive blood testing on four occasions over 3 months. The variability of each test over time will be calculated. On the basis of these results, tests will be selected for a future study of the effects of HRT. So far we have screened 160 women and have identified 23 who have entered the sequential testing phase of the protocol.